The objectives of these studies are to define which subcellular constituents of animal and human granulocytes possess biologically active substances affecting blood coagulation, to determine if subcellular fractions of macrophages have these same biological activities, and to examine the influence of endotoxin and certain drugs on the procoagulant activity of leukocytes. Blood leukocytes will be isolated by dextran sedimentation and differential centrifugation on ficoll-hypaque gradients. Lysosomes will be obtained from disrupted cells by differential centrifugation and separated into distinct populations on linear sucrose density gradients; these will be monitored by light and electronmicroscopy. Soluble extracts of lysosomes will be separated by column chromatography, electrofocusing and gel electrophoresis into purified fractions for characterization and biological testing. BIBLIOGRAPHIC REFERENCE: H.I. Saba, J.C. Herion, R.I. Walker and H.R. Roberts: Effect of Lysosomal Cationic Proteins from Polymorphonuclear Leukocytes upon the Fibrinogen and Fibrinolysis System. Thrombosis Research 7:543-554, 1975.